The proposed studies are designed to enhance our understanding of the pathogenesis of central nervous system (CNS) injury in SLE focusing primarily on the role of humoral antibodies. The accumulated evidence concerning tissue injury in SLE patients with CNS disease suggests that immune complexes are not direct mediators of tissue injury. The relationship to disease and specificity of antibodies reactive with neurons, T cells and B cells will be evaluated. In addition, an attempt will be made to detect humoral antibodies to synaptosomes, cytoplasmic antigens of glial and neuronal origin and brain capillaries. Brain tissue from autopsied patients will be eluted to determine if humoral antibodies and/or immune complexes selectively localize in vivo in brain tissue. Indirect immunofluorescence, cytotoxicity, and crossed immunoelectrophoresis will be utilized with substrates of brain tissue, neural cell cultures and isolated brain antigens for the detection of antibodies. The significance of immune complex deposits in choroid plexus will be evaluated to determine if these deposits correlate with clinical CNS disease and if choroid plexus injury enhances the diffusion of antibodies into the cerebrospinal fluid. The diagnostic and pathogenetic significance of the high incidence of anti-Sm antibodies as well as other non-organ specific antibodies in SLE patients with CNS disease will be evaluated. Direct immunofluorescence will be performed on brain tissue to determine if a correlation between immunoglobulin and complement deposits, tissue injury and clinical symptoms exists.